title: Depletion of gammadelta+ T cells increases CD4+ FoxP3 (T regulatory) cell response in coxsackievirus B3-induced myocarditis.
abstract: Coxsackievirus B3 (CVB3) causes severe myocarditis in BALB/c mice which depends upon CD4(+) T helper type 1 [Th1; i.e. interferon-gamma(+) (IFN-gamma(+))] and gammadelta(+) cells. Depleting gammadelta(+) cells using anti-gammadelta antibody suppresses myocarditis and CD4(+) IFN-gamma(+) cell numbers in the spleen and heart of infected mice while increasing CD4(+) FoxP3(+) cells. Mice deficient in gammadelta(+) cells have increased numbers of naïve (CD44(lo) CD62L(hi)) and fewer effector (CD44(hi) CD62(lo)) memory CD4(+) cells than infected gammadelta(+)-cell-sufficient mice. Virus neutralizing antibody titres are not significantly different between gammadelta(+) T-cell-sufficient and -deficient animals. To confirm that the memory cell response differs in acutely infected mice lacking gammadelta(+) cells, CD4(+) cells were purified and adoptively transferred into naïve recipients, which were rested for 4 weeks then infected with CVB3. Recipients given either 0.5 x 10(6) or 1.0 x 10(6) CD4(+) from infected donors developed over twice the severity myocarditis and 10-fold less cardiac virus titre compared with recipients given equivalent numbers of CD4(+) cells from infected and gammadelta(+)-cell-depleted donor animals. Additionally, to show that more functionally active T regulatory cells are present in gammadelta(+) T-cell-depleted mice, CD4(+) CD25(+) and CD4(+) CD25(-) cells were isolated and adoptively transferred into infected recipients. Mice receiving CD4(+) CD25(+) cells from gammadelta(+) T-cell-depleted donors developed significantly less myocarditis and CD4(+) Th1 cell responses compared with mice receiving equal numbers of CD4(+) CD25(+) cells from infected gammadelta(+) T-cell-sufficient animals. This study shows that gammadelta(+) cells promote CD4(+) IFN-gamma(+) acute and memory responses by limiting FoxP3(+) T regulatory cell activation.
authors: Department of Pathology, University of Vermont, Colchester, VT 05446, USA. sally.huder@uvm.edu
authors: Sally A
authors: SA
authors: Huber
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D003384:Coxsackievirus Infections / Q000276:immunology* / Q000473:pathology; D029822:Enterovirus B, Human; D051858:Forkhead Transcription Factors / Q000032:analysis*; D018960:Hyaluronan Receptors / Q000378:metabolism; D007156:Immunologic Memory / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D019041:L-Selectin / Q000378:metabolism; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000276:immunology* / Q000473:pathology / Q000821:virology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: C476399:Cd44 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018960:Hyaluronan Receptors; C508018:Il2ra protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D016692:Receptors, Antigen, T-Cell, gamma-delta; D019041:L-Selectin