T cells from BB-DP rats show a unique cytokine mRNA profile associated with the IDDM1 susceptibility gene, Lyp.
Diabetes prone biobreeding rats display several abnormalities in T cell numbers, T cell function and T cell surface phenotype which are associated with the onset of spontaneous disease. One of the most pronounced abnormalities in these animals is a marked T cell lymphopenia which is evident in both CD4+ and CD8+ peripheral T cell subsets. To gain a better understanding as to the nature of T cell responses in these animals, we have utilized RT-PCR to analyze the cytokine mRNA profiles of mitogen activated peripheral T cells derived from lymphopenic and non-lymphopenic animals. Our results suggest that inheritance of the lymphopenia gene, Lyp, is associated with a unique cytokine profile most similar to that previously described for mouse medullary thymocytes. In addition, cell surface staining of peripheral T cells from diabetes prone animals revealed a high frequency of Thyl+ cells, which is characteristic of both thymocytes and recent thymic emigrants. Following thymectomy, T cell responsiveness to a number of different stimuli is greatly reduced on a cell for cell basis as is the absolute number of surviving T cells. Taken collectively, our results suggest that the majority of the peripheral T cell pool in these diabetic prone rats consists of short lived, recent thymic emigrants which most likely also contain the effector cells required for initiation of diabetes.
Gold
D P
DP
Sidney Kimmel Cancer Center, San Diego, CA 92121, USA.
Shaikewitz
S T
ST
Mueller
D
D
Redd
J R
JR
Sellins
K S
KS
Pettersson
A
A
Lernmark
A
A
Bellgrau
D
D
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D004198:Disease Susceptibility; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D015848:Interleukin-5 / Q000096:biosynthesis / Q000235:genetics; D015810:Linkage Disequilibrium / Q000235:genetics*; D008231:Lymphopenia / Q000235:genetics*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D011913:Rats, Inbred BB; D013934:Thymectomy / Q000009:adverse effects
D016207:Cytokines; D007376:Interleukin-2; D015848:Interleukin-5; D012333:RNA, Messenger; D007371:Interferon-gamma