Type 2 immune deviation has differential effects on alloreactive CD4+ and CD8+ T cells.
Allograft rejection has been associated with detection of the type 1 lymphokines, IFN-gamma and IL-2. The role of type 2 cytokines (IL-4 and IL-5) remains controversial, as is whether alloreactive CD4+ and CD8+ T cells behave similarly when exposed to type 2 cytokine-enhancing manipulations. We studied the characteristics of alloreactive CD4+ and CD8+ T cells before and after type 2 immune deviation induced by IL-4 plus anti-IFN-gamma Ab. Alloreactive T cells from naive mice were low in frequency, produced only IL-2, and were predominantly CD4+, while alloreactive T cells from allograft-primed mice were high in frequency, produced IFN-gamma, IL-2, and IL-4, and were predominantly CD8+. Type 2 immune deviation of allospecific CD4+ T cells resulted in IL-4 and IL-5 production without IFN-gamma, consistent with unipolar type 2 immunity. These T cells mediated delayed-type hypersensitivity, but not cytotoxicity. Under identical type 2 cytokine-inducing conditions, allospecific CD8+ T cells were primed to become IL-4, IL-5, and IFN-gamma producers, and exhibited cytotoxicity, but not classic delayed-type hypersensitivity. Adoptive transfer of either cell population into SCID recipients of allogeneic skin resulted in graft rejection, with stable allospecific type 2 cytokine production in vivo. Adoptive transfer of the IL-4/IL-5-producing CD4+ T cells, but not the CD8+ T cells, induced a distinct histopathology characterized by marked eosinophilic infiltration of the skin. We conclude that type 2 immune deviation has differential effects on CD4+ and CD8+ T cells and results in emergence of alternate effector mechanisms capable of destroying allografts.
Matesic
D
D
Department of Medicine, Cleveland Veterans' Affairs Medical Center, OH 44106, USA.
Valujskikh
A
A
Pearlman
E
E
Higgins
A W
AW
Gilliam
A C
AC
Heeger
P S
PS
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D007114:Immunization; D007376:Interleukin-2 / Q000096:biosynthesis; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D016038:Skin Transplantation / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D014184:Transplantation, Homologous
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D007376:Interleukin-2; D007519:Isoantigens