Naive and Memory T Cell Subsets are Differentially Mobilized During Physical Stress

Abstract

This study examined the naive and memory phenotypic profiles of CD4⁺ and CD8^hi T cells that were mobilized to the peripheral circulation during a combination of aerobic exercise and heat stress, determining expression of the adhesion molecules CD62L and CD11a on the recruited cells. Twelve recreationally active males (age 27.1 ± 5.3 yr, height 1.77 ± 0.08 m, mass 76.9 ± 12.0 kg, V˙O₂peak 43.9 ± 6.7 mL × kg^-1 × min^-1) completed a 40 min bout of cycle ergometry at 65 % of V˙O₂peak while immersed to mid-chest in a water bath at 39 °C. Venous blood samples were collected before (T₀), during (T₄₀) and 30 min after (T₇₀) exposure to combined exercise and heat stress. Specimens were analyzed by three-colour flow cytometry for CD4⁺ and CD8^hi T cell expression of CD45RO, CD11a and CD62L. Some 80 % of the CD4⁺ T cells that were mobilized were of the CD45RO memory phenotype, with the numbers of CD11a^lo and CD62L⁺ cells increasing more than those of CD11a^hi and CD62L^- cells. For the CD8^hi cells, there was a more equal recruitment of CD45RO^- naive (43 %) and CD45RO⁺ memory (57 %) cells. The majority (84 %) of recruited CD8⁺ cells were CD11a^hi; there was a trend to predominance of CD62L^- cells (57 %) for the memory subset, but with almost equal recruitment of CD62L^+/- for the naive subset. We conclude that the exercise + heat stress induced trend to an increase in CD4⁺ T cells is linked in some way to memory phenotype; it cannot be explained simply by a high density expression of CD11a and lack of the lymph node homing receptor (CD62L). Furthermore, although mobilization of CD8^hi T cells is not linked to memory phenotype, a high density expression of CD11a and a lack of the lymph node homing receptor are important determinants of CD8^hi T cell mobilization.

Key words

Adhesion molecules - exercise immunology - lymphocyte mobilization - anti-inflammatory T cells

References

• 1 Akbar A N, Terry L, Timms A, Beverley C L, Janossy G. Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells.  J Immunol. 1988;  140 2171-2178
• 2 Austrup F, Vestweber D, Borges E, Lohning M, Brauers R, Herz U. P- and E-selectin mediate recruitment of T-helper-1 but not T-helper-2 cells into inflamed tissues.  Nature . 1997;  385 81-83
• 3 Bell E B, Sparshott S M. Interconversion of CD45R subsets of CD4 T cell in vivo.  Nature . 1990;  348 163-166
• 4 Berg M, Murakawa Y, Camerini D, James S P. Lamina propria lymphocytes are derived from circulating cells that lack the Leu-8 lymph node homing receptor.  Gasteroenterol. 1991;  101 90-99
• 5 Bottomly K. A functional dichotomy in CD4+ T lymphocytes.  Immunol Today. 1988;  9 268-274
• 6 Brenner I KM, Shek P N, Shephard R J. Heat exposure and immune function: Potential contributions to the immune response.  Exerc Immunol Rev. 1995;  1 49-80
• 7 Butcher E C, Picker L J. Lymphocyte homing and homeostasis.  Science. 1996;  272 60-66
• 8 Byrne J A, Butler J L, Cooper M D. Differential activation requirements for virgin and memory T cells.  J Immunol. 1988;  141 3249-3257
• 9 Clement L, Yamashita N, Martin A. The functionally distinct subpopulations of human CD4⁺ helper/inducer T lymphocytes defined by anti-CD45R antibodies derive sequentially from a differentiation pathway that is regulated by activation-dependent post-thymic differentiation.  J Immunol. 1988;  141 1464-1470
• 10 Constant S L, Bottomly K. Induction of TH1 and TH2 CD4⁺ T cell responses: The alternative approaches.  Ann Rev Immunol. 1997;  15 297-322
• 11 De Jong R, Brouwer M, Miedema F, Van Lier R AW. Human CD8⁺ T lymphocytes can be divided into CD45RA⁺ and CD45RO⁺ cells with different requirements for activation and differentiation.  J Immunol. 1991;  146 2088-2094
• 12 Dhabhar F S, Miller A H, McEwen B S, Spencer R L. Effects of stress on immune cell distribution: dynamics and hormonal mechanisms.  J Immunol. 1995;  154 5511-5527
• 13 Dill D B, Costill D L. Calculation of percentage changes in volumes of blood, plasma and red cells in dehydration.  J Appl Physiol. 1974;  37 247-248
• 14 Foster N K, Martyn J B, Rangno R E, Hogg J C, Pardy R L. Leukocytosis of exercise: role of cardiac output and catecholamines.  J Appl Physiol. 1986;  61 2218-2223
• 15 Fujii Y, Okumura M, Inada K, Nakahara K. Reversal of CD45 isoform switching in CD8⁺ T cells.  Cell Immunol. 1992;  139 176-184
• 16 Gabriel H, Kindermann W. Flow cytometry: principles and applications in exercise immunology.  Sports Med. 1995;  20 302-320
• 17 Gabriel H, Schmitt B, Urhausen A, Kindermann W. Increased CD45RA⁺CD45RO⁺ cells indicate activated T cells after endurance exercise.  Med Sci Sports Exerc. 1993;  25 1352-1357
• 18 Gabriel H, Schwarz L, Born P, Kindermann W. Differential mobilization of leukocyte and lymphocyte subpopulations into the circulation during endurance exercise.  Eur J Appl Physiol. 1992;  65 529-534
• 19 Gabriel H, Urhausen A, Kindermann W. Circulating leucocyte and lymphocyte subpopulations before and after intensive endurance exercise to exhaustion.  Eur J Appl Physiol. 1991;  63 449-457
• 20 Gallatin M, John T PS, Siegelman M, Reichart R, Butcher E C, Weissman I L. Lymphocyte homing receptors.  Cell. 1985;  44 673-680
• 21 Gallatin W M, Weissman I L, Butcher E C. A cell-surface molecule involved in organ-specific homing of lymphocytes.  Nature. 1983;  304 30-34
• 22 Gannon G A, Rhind S G, Shek P N, Shephard R J. Differential cell adhesion molecule expression and lymphocyte mobilisation during prolonged aerobic exercise.  Eur J Appl Physiol. 2001;  84 272-282
• 23 Jung T M, Gallatin W M, Weissman I L, Dailey M O. Down-regulation of homing receptors after T cell activation.  J Immunol. 1988;  141 4110-4117
• 24 Kanegane H, Kasahara Y, Niida Y, Yachie A, Sughii S, Takatsu K, Taniguchi N, Miyawaki T. Expression of L-selectin (CD62L) discriminates Th1 and Th2-like cytokine-producing memory CD4⁺ T cells.  Immunol. 1996;  87 186-190
• 25 Klonz A, Wonigeit K, Pabst R, Westermann J. The marginal blood pool of the rat contains not only granulocytes, but also lymphocytes, NK cells and monocytes: a second intravascular compartment, its cellular composition, adhesion molecule expression and interaction with the peripheral blood pool.  Scand J Immunol. 1996;  44 461-469
• 26 Kurokawa Y, Shinkai S, Torii J, Hino S, Shek P N. Exercise-induced changes in the expression of surface adhesion molecules on circulating granulocytes and lymphocyte subpopulations.  Eur J Appl Physiol. 1995;  71 245-252
• 27 Landay A L, Muirhead K A. Procedural guidelines for performing immunophenotyping by flow cytometry.  Clin Immunol Immupathol. 1989;  52 48-60
• 28 Lanier L L, Phillips J H, Hackett J, Tutt M, Kumar V. Natural killer cells: definition of a cell type rather than function.  J Immunol. 1986;  137 2735-2739
• 29 Mackay C R. Homing of naive, memory and effector lymphocytes.  Curr Opin Immunol. 1993;  5 423-427
• 30 Mackay C R, Marston W L, Dudler L. Naive and memory T cells show distinct pathways of lymphocyte recirculation.  J Exp Med. 1990;  171 801-817
• 31 Mosmann T R, Coffman R L. Heterogeneity of cytokine secretion patterns and functions of helper T cells.  Adv Immunol. 1989;  46 111-147
• 32 Mosmann T R, Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more.  Immunol Today. 1996;  17 138-146
• 33 Okumura M, Fujii Y, Inada K, Nakahara K, Matsuda H. Both CD45RA⁺ and CD45RA^- subpopulations of CD8⁺ T cells contain cells with high levels of lymphocyte function-associated antigen-1 expression, a phenotype of primed T cells.  J Immunol. 1993;  150 429-437
• 34 Oppenheimer-Marks N, Davis L, Lipsky P E. Human T lymphocyte adhesion to endothelial cells and transendothelial migration.  J Immunol. 1990;  145 140-148
• 35 Pabst R, Binns R M. Heterogeneity of lymphocyte homing physiology: Several mechanisms operate in the control of migration to lymphoid and non-lymphoid organs in vivo.  Immunological Reviews. 1989;  108 83-109
• 36 Picker L, Treer J, Ferguson-Darnell B, Collins P, Bergstresser P, Terstappen L. Control of lymphocyte recirculation in man: 2. Diffferential regulation of the cutaneous lymphocyte-associated antigen, a tissue selective homing receptor for skin-homing T-cells.  J Immunol. 1993;  150 1122-1136
• 37 Picker L, Treer J, Ferguson-Darnell B, Collins P, Buck D, Terstappen L. Control of lymphocyte recirculation in man. 1. Differential regulation of the peripheral lymph node homing receptor L-selectin on T cells during the virgin to memory cell transition.  J Immunol. 1993;  150 1105-1121
• 38 Picker L J, Terstappen L W, Rott L S, Streeter P R, Stein H, Butcher E C. Differential expression of homing-associated adhesion molecules by T cell subsets in man.  J Immunol. 1990;  145 3247-3255
• 39 Prince H E, York J, Jensen E R. Phenotypic comparison of the three populations of human lymphocytes defined by CD45RO and CD45RA expression.  Cell Immunol. 1992;  145 254-262
• 40 Rhind S G, Gannon G A, Shek P N, Brenner I KM, Zamecnik J, Buguet A, Natale V M, Shephard R J, Radomski M W. Contribution of exertional hyperthermia to sympathoadrenal-mediated lymphocyte subset redistribution.  J Appl Physiol. 1999;  87 1178-1185
• 41 Romagnani S. The Th1/Th2 paradigm.  Immunol Today. 1997;  18 263-267
• 42 Sallusto F, Mackay C R, Lanzavecchia A. Selective expression of the eotaxin receptor CCR3 by human T helper 2 cells.  Science. 1997;  277 2005-2007
• 43 Saltini C, Trapnell B C, Tamura N, Crystal R G. Biased accumulation of T lymphocytes with ‘memory'-type CD45 leucocyte common antigen gene expression on the epithelial surface of the human lung.  J Exp Med. 1990;  171 1123-1140
• 44 Sanders M E, Makgoba M W, Sharrow S O, Stephany D, Springer T A, Shaw S. Human memory T lymphocytes express increased levels of three cell adhesion molecules (LFA-3, CD2, and LFA-1) and three other molecules (UCHL1, CDw29, and Pgp-1) and have enhanced IFN-gamma production.  J Immunol. 1988;  140 1401-1407
• 45 Schweighoffer T, Tanaka Y, Tidswell M, Erle D J, Horgan K J, Ginther Luce G E, Lazarovits A I, Buck D, Shaw S. Selective expression of integrin alpha-4 beta-7 on a subset of human CD4+ memory T cells with hallmarks of gut-trophism.  J Immunol. 1993;  151 717-729
• 46 Stamper H B, Woodruff J J. Lymphocyte homing into lymph nodes: in vitro demonstration of the selective affinity of recirculating lymphocytes for high endothelial venules.  J Exp Med. 1976;  144 828-833
• 47 Tedder T F, Penta A C, Levine H B, Freedman A S. Expression of the human leukocyte adhesion molecule, LAM1. Identity with the TQ1 and Leu-8 differentiation antigens.  J Immunol. 1990;  144 532-540
• 48 Tsuji T, Nibu R, Iwai K, Kanegane H, Yachie A, Seki H, Miyawaki T, Tanaguchi N. Efficient induction of immunoglobulin production in neonatal naive B cells by memory CD4⁺ T cell subset expressing homing receptor L-selectin.  J Immunol. 1994;  152 4417-4424
• 49 Yamashita N, Clement L T. Phenotypic characterization of the post-thymic differentiation of human alloantigen-specific CD8⁺ cytotoxic T lymphocytes.  J Immunol. 1989;  143 1518-1523
• 50 Youseffi-Etemad R, Axelsson B. Parallel pattern of expression of CD43 and of LFA-1 on the CD45RA⁺ (naive) and CD45RO⁺ (memory) subsets of human CD4⁺ and CD8⁺ cells. Correlation with the aggregative response of the cells to CD43 monoclonal antibodies.  Immunol. 1996;  87 439-446