Immune responses to polyclonal T-cell vaccination in patients with progressive multiple sclerosis

Figures & data

Table 1. Clinical characteristics of MS patients (n = 39).

№.	Age, gender (F, M)	Disease duration (years)	EDSS
1	32, F	15	6.0
2	33, F	14	3.5
3	25, F	7	5.0
4	47, F	14	6.5
5	29, F	4	4.5
6	30, F	3	4.0
7	27, M	8	7.0
8	30, F	11	5.0
9	40, M	15	7.0
10	46, F	8	5.5
11	53, M	9	6.0
12	23, F	7	6.0
13	43, F	7	4.0
14	29, F	9	5.0
15	33, F	3	6.0
16	51, F	13	6.0
17	26, M	7	6.5
18	31, M	6	6.0
19	29, F	11	6.5
20	44, M	9	5.5
21	26, F	10	2.5
22	37, F	7	7.0
23	26, M	8	3.5
24	33, F	11	4.5
25	36, F	12	2.5
26	47, F	9	4.5
27	48, M	13	7.0
28	43, F	15	2.5
29	40, F	8	2.5
30	40, M	7	5.0
31	25, F	6	5.0
32	30, F	10	2.0
33	54, F	15	6.5
34	49, F	13	4.5
35	46, F	15	2.5
36	26, M	5	6.5
37	29, F	8	4.0
38	23, F	6	2.5
39	40, F	10	4.0

The neurological status of each patient was evaluated using the Kurtzke expanded disability status scale (EDSS, Expanded Disability Status Scale, range 0.0 = normal neurological status to 10.0 = death due to MS) following protocols outlined by the National MS Society.

Table 2. Contents of memory T-cell subsets.

T-cell subset	Healthy persons	MS patients pre-treat	TCV-treated patients
CD4^+	45.46 ± 3.27	40.67 ± 1.39	35.66 ± 3.13
CD4^+CD45RO^+CD62L^+	1.11 ± 0.48	4.89 ± 0.56*	3.35 ± 0.94
CD4^+CD45RO^+CD62L^-	9.28 ± 4.16	7.64 ± 1.38	8.65 ± 2.58
CD4^+CD45RO^-CD62L^+	10.18 ± 3.86	6.55 ± 0.54	9.09 ± 2.61
CD4^+CD45RO^-CD62L^-	24.1 ± 5.7	19.06 ± 3.79	14.78 ± 4.11
CD8^+	18.1 ± 1.12	21.98 ± 3.25*	15.41 ± 2.80
CD8^+CD45RO^+CD62L^+	0,1 ± 0,03	0.37 ± 0,10*	0.52 ± 0.18
CD8^+CD45RO^+CD62L^-	0.31 ± 0.07	1.28 ± 0.30*	1.45 ± 0.34
CD8^+CD45RO^-CD62L^+	3.93 ± 1.29	4.67 ± 1.37	2.78 ± 0.86
CD8^+CD45RO^-CD62L^-	11.47 ± 1.77	14.61 ± 2.32	9.91 ± 2.02

Percentages of total number of lymphocytes (means ± SEM) in healthy persons (n = 10) and MS patients (n = 11).

* p < .05 vs. in healthy persons.

Table 3. Frequencies of T-cell subsets.

T-subset	Healthy persons	MS patients, pre- treat	TCV-treated patients
CD4^+/CD45RO^+/IFNγ^+/IL4^-	3.73 ± 0.85	8.60 ± 3.64*	3.72 ± 1.23**
CD4^+/CD45RO^+/IFNγ^-/IL4^+	3.00 ± 0.91	2.68 ± 1.09	1.53 ± 0.49
CD4^+/CD45RO^+/IFNγ^+/IL4^+	0.79 ± 0.18	8.69 ± 4.91*	1.41 ± 1.01**
CD4^+/CD45RO^-/IFNγ^+/IL4^-	1.28 ± 0.35	1.93 ± 0.90*	0.95 ± 0.80**
CD4^+/CD45RO^-/IFNγ^-/IL4^+	0.54 ± 0.14	0.96 ± 0.29	0.39 ± 0.13
CD4^+/CD45RO^-/IFNγ^+/IL4^+	0.81 ± 0.18	0.48 ± 0.22	0.31 ± 0.13
CD8^+/CD45RO^+/IFNγ^+/IL4^-	0.34 ± 0.12	11.10 ± 4.23*	5.87 ± 1.84**
CD8^+/CD45RO^+/IFNγ^-/IL4^+	2.89 ± 0.74	4.39 ± 2.48	2.01 ± 1.16
CD8^+/CD45RO^+/IFNγ^+/IL4^+	0.42 ± 0.08	1.47 ± 0.84*	0.79 ± 0.40
CD8^+/CD45RO^-/IFNγ^+/IL4^-	0.27 ± 0.11	7.48 ± 2.09*	3.42 ± 1.20
CD8+/CD45RO^-/IFNγ^-/IL4^+	1.13 ± 0.30	1.43 ± 0.56	0.69 ± 0.27
CD8^+/CD45RO^-/IFNγ^+/IL4^+	0.30 ± 0.05	0.74 ± 0.25	0.45 ± 0.19

Percentages of total number of lymphocytes (means ± SEM)) producing intracellular IFNγ and IL-4 in healthy persons (n = 12) and MS patients (n = 10).

* p < .05 vs. healthy persons

** p < .05 vs. values before TCV-based treatment.

Figure 1. Myelin-induced proliferative responses by PBMC from MS patients. PMBC were isolated from MS patients (n = 19; 5 male, 14 female) before and 1 year after onset of TCV-based treatment. In this assay, at each timepoint, PBMC were cultured without or with myelin-associated antigens for 5 days and then assessed for proliferative responses (in terms of cpm). Values shown are means (± SD) cpm. ^#Value significantly different between cultures with and without myelin-associated (p < .05). *Value significantly different between data before and after TCV-based treatment (p < .05).

Table 4. Plasma cytokine levels.

		Time after T-cell vaccination
Cytokine	Pre-treatment value	6 months	12 months	24 months
IFNγ	144 ± 46	182 ± 82	44 ± 30*	25 ± 13*
IL-17	8 ± 4	7 ± 2	6 ± 2	6 ± 2
IL-18	92 ± 11	67 ± 9	112 ± 24	96 ± 9
IL- 4	12 ± 3	17 ± 4	26 ± 11*	77 ± 34*
IL-10	4 ± 1	4 ± 1	2 ± 1	12 ± 4*

Values are reported in pg/ml (means ± SEM) in samples from MS patients (n = 19) in the course of T-cell vaccination.

* p < .05 vs. cytokine levels before immunotherapy.